Reactome | ACLY tetramer transforms CIT to Ac-CoA

ACLY tetramer transforms CIT to Ac-CoA

Stable Identifier

R-HSA-75848

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

ATP + citrate + CoA => acetyl-CoA + ADP + oxaloacetate + phosphate, Generation of Cytoplasmic Acetyl CoA from Citrate

ReviewStatus

5/5

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While fatty acid synthesis from acetyl CoA (Ac-CoA) proceeds in the cytosol, most Ac-CoA in the cell is generated within the mitochondria by oxidative decarboxylation of the pyruvate derived from glycolysis, as well as from several reactions of amino acid catabolism. Mitochondrial Ac-CoA is transported to the cytosol as citrate (CIT) to participate in fatty acid biosynthesis (for a review, see, e.g., Arnold & Finley, 2023). Cytosolic ATP-citrate synthase (ACLY), in tetrameric form, catalyzes the transformation of CIT to Ac-CoA and plays an essential role in lipogenesis, adipogenesis, and differentiation of 3T3-L1 preadipocyte cells (Elshourbagy et al. 1992, Sun et al., 2011; Lin et al. 2013). Cytosolic MORC family CW-type zinc finger protein 2 (MORC2) positively regulates the activity of ACLY. Thus, it could mediate lipogenesis, adipogenic differentiation, and lipid homeostasis (Sanchez-Solana et al. 2014). High glucose leads to overexpression and nuclear localization of ACLY, subsequently increasing histone acetylation (reviewed by Bradshaw, 2021). SLC25A1 citrate export and acetyl-CoA production by ACLY are sometimes called the citrate-malate shuttle (for a review, see Guo et al., 2023).

Literature References

PubMed ID	Title	Journal	Year
33917812	Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan Bradshaw, PC	Antioxidants (Basel)	2021
24286864	Cytosolic functions of MORC2 in lipogenesis and adipogenesis Kumar, R, Sánchez-Solana, B, Li, DQ	Biochim. Biophys. Acta	2014
37051670	Determiners of cell fates: the tricarboxylic acid cycle versus the citrate-malate shuttle Meng, Y, Lu, Z, Luo, S, Guo, D, He, H	Protein Cell	2023
36581208	Regulation and function of the mammalian tricarboxylic acid cycle Arnold, PK, Finley, LWS	J Biol Chem	2023
23932781	Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth Xiong, Y, Guan, KL, Zhou, X, Gao, X, Lei, QY, Lin, R, Li, T, Tao, R	Mol. Cell	2013
1371749	Cloning and expression of a human ATP-citrate lyase cDNA Gloger, IS, Elshourbagy, NA, Wells, TN, Franklin, M, Saxty, BA, Hughes, SA, Groot, PH, Kmetz, PJ, Near, JC	Eur J Biochem	1992
22102020	ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase Sun, T, Fraser, ME, Hayakawa, K	Acta Crystallogr Sect F Struct Biol Cryst Commun	2011